Hi, I'm Maureen Canectel. I've been a cardiology PA since 2005, and I've worked in cardiac electrophysiology since 2008. I transitioned to full-time PA education in 2016, where I really enjoy teaching modules specific to cardiology and cardiac electrophysiology. I'm very excited to be here with you today as part of MedAxium to deliver an educational series about cardiac electrophysiology and topics specific to that. So let's get started. Welcome to our first offering in the series, Electrophysiology for the Cardiovascular Advanced Practice Provider. I wanted to start the series by talking a little bit about the anatomy and physiology of the cardiac conduction system. I have a few readings here that you will probably find helpful as we work through the material. In general, I want to focus on the anatomy of the cardiac conduction system, the components of the cardiac action potential, and apply changes in depolarization and repolarization to cardiac rhythm disturbances. The focus here is I want to bring your attention back to the physiology and the pathophysiology of what takes place within the cardiac system. I also want to focus on how the medications that we use have certain effects that can be good or, in some ways, potentially bad. We'll talk about why that is that that happens. The first thing to think about is the overall anatomy, and that starts with the sinus node. We have the sinus node, which has an intrinsic beating of 60 to 100 beats per minute. From there, we have the AV node, the bundle of his, bundle branches, and the Purkinje fibers as we work through from top to bottom of the heart. The electrical cascade begins with the stimulation of individual myocytes and continues on through specialized areas of conducting tissue. The sinus node always starts the impulse as long as it's the fastest pacemaker, but at any point in time, cells in the AV node as well as the Purkinje fibers can become the predominant pacemaker if everything above fails. This is important to consider when you're evaluating a patient with, for instance, complete heart block or near syncope or syncope, and maybe in the emergency department. If you see an EKG that shows complete heart block, but the ventricular rate is maybe 30 beats per minute and the QRS is very wide, that should tell you that the AV node is failing to conduct impulses, and the AV node is also failing to become the dominant pacemaker. What we're left with are the Purkinje fibers becoming the dominant pacemaker. That means that there's nothing else below there that can take over if that fails. It's important to consider this cascade of electrical events as you're evaluating a patient with a conduction disturbance. Cells with the fastest rate of depolarization become the dominant pacemaker, and this normally starts in the sinus node. If the sinus node fails, the AV node takes over. If that fails, the Purkinje fibers are the last resort. These cells only demonstrate automaticity if everything above them fails, and this is an important consideration because we're going to start breaking down now things like the working cells of the heart and the conducting cells of the heart because they work differently. The working cells are the cardiac myocytes that contract. Their main job is to contract, and that's why we call them the working cells. The majority of cells in the heart are working cells, and they are predominantly in the ventricles. The conducting cells are pockets of cells that conduct electricity located in the sinus node, the AV node, as well as the Purkinje fibers. The sinus node includes normal pacemaker cells. The AV node is the electrical gateway between the atria and the ventricles, and the Purkinje fibers are a specialized electrical distribution network. It's located in the subendocardial space. Although all cells in the heart have some capability to conduct action potential, some cells are specialized for generating and propagating electrical signals through the heart, and those are the ones that we call conducting cells. They have relatively few myofilaments, and they generate only weak contractile forces, and part of this is because they have a very different action potential. The division of labor can be thought of as working cells and conducting cells. I've got the Purkinje fibers listed there as working cells because they do have some automaticity, which makes them a little bit different from the other working cells. They have a very fast and a very long action potential. When you think back to what you've learned about the action potential, it probably looks like that top picture there. That's what you're used to seeing. All-to-no automaticity in an action potential is initiated by a large sodium current, which stimulates then calcium channels, resulting in a long plaque toe phase in the action potential when calcium enters the cells and causes contraction of the muscle. The sinus node and the AV node, very different. They have a short and a slow action potential, and they have this constant phase of automaticity. What happens here is in the sinus node and the AV node cells, the lines aren't flat. Let me get my laser pointer here and point this out. If you can see where my mouse is here, there's no flat line along here in phase four. This is interesting to point out because there's just this spontaneous depolarization and repolarization as it moves towards a net inward current, getting closer and closer to that threshold, making the cell more positive before it can depolarize. This is very different from the action potential up top here, where it happens very quickly. The medications that we use will target different components of each one of these action potentials. In the sinus node and the AV node, we use things like beta blockers and calcium channel blockers, which can affect automaticity, and also this calcium channel opening that occurs, which results really in the action potential in the sinus node and the AV node. In the working cells, we use things like sodium channel blockers or potassium channel blockers to change that action potential and decrease re-entry into a cell. More on that here in a minute. Let's talk a bit more about those working cells. The resting membrane potential of ventricular cells is very negative. It's minus 90 millivolts. When sodium channels open, which are positive, the cell voltage becomes more positive and we rise closer to threshold. This results in depolarization or contraction. When we reach a plateau phase, this is when calcium begins to be released from sarcoplasmic reticulum during contraction. The action potential terminates as potassium channels open and that positive potassium leaves the cell, resulting in a more negative balance and repolarization occurs. I like this picture because it shows you how everything looks lined up relative to one another. It also shows you how that lines up with the EKG. A lot of these things we talk about with the cardiac conduction and action potentials, they're very abstract. It's hard to really visualize that. We all feel pretty good about looking at an EKG strip and what a P wave and a QRS and a T wave means. If we go back over to this picture here, we can see how those line up. Notice the sinus node and the AV node, the very different appearing action potential from things like atrial, Purkinje fiber, epicardium. Those areas are more like the traditional action potential that we're used to seeing. You can see how that lines up more with depolarization, our classic depolarization we think about with a QRS complex. Let's discuss in a bit more detail the cardiac action potential. In phase zero, sodium channels open. Now we're looking at that action potential for our working cells, which is what happens in most of the cells in the heart. Phase zero, sodium channels open and there's a rapid upstroke as we get closer and closer to that depolarization threshold. In phase one, we start to have more of a potassium efflux. Potassium efflux is from the cell and the cell begins to repolarize just a bit. Then we start with our plateau phase where potassium continues to efflux and calcium begins to influx into the cell. That plateau phase results because we're at a little bit of a balance there. When calcium enters, contraction occurs and now we have systole. Phase three begins when potassium efflux exceeds calcium influx. The result of this is the cell repolarizes back on its way to phase four when it again achieves a resting state and a negative membrane potential, or you can think about this as diastole. What's interesting here, we think about what we've already discussed, is that in pacemaker cells, nothing really happens in phase one and phase two. We don't talk about that with those cells because they're not contractile cells. They just essentially depolarize and repolarize over and over. We have that sinus node automaticity and AB conduction that happens as a result. The next phase we need to discuss is the refractory period. The absolute refractory period, when this occurs, the cell is completely unexcitable to a new stimulus. This occurs because sodium channels are closed. This renders the heart essentially unresponsive to any stimuli that can occur. Regardless of the strength of the stimulus, the cells can't respond to this. That's the absolute refractory period, which occurs when, think of it like the train has already started down the track and there's nothing that you can do to stop it until it gets to where it's going. That's the absolute refractory period. If you think about how this correlates in this picture, we can think of how it correlates to the QRS complex. This is kind of like when ... It's an important concept in atrial fibrillation, for example. This is a great clinical correlate. In atrial fibrillation, the AB node has principles of refractoriness. It's a really fascinating concept that prevents the heart, the ventricular rate, from being really, really fast. This is why the atria are going to beat at maybe 300 beats per minute in atrial fibrillation, but thankfully the ventricles don't beat that fast. That's because no matter how hard you try and stimulate and create another impulse, during that refractory period, it doesn't happen. It's a really neat safety valve that we have within our heart to prevent ventricular rates from being excessively high under normal circumstances. That's the absolute refractory period. If you look here in this picture, the relative refractory period is this short period of time that follows the absolute refractory period. During this time, it's possible for a second action potential to be initiated, but the stimulus must be larger than normal. If you look at this picture, what that lines up with, it lines up really with the end of that T wave. If someone has a prolonged QT interval, we're going to prolong the refractory period, but it doesn't really matter what we do to the absolute refractory period. We care about that relative refractory period. When prolonging a QT interval, you're going to prolong that relative refractory period as well. This is where bad things can happen. Clinical correlation here would be if you've got someone with a long QT interval, let's say their potassium is low and they're bradycardic and their QT starts drawing out. Normally, if another impulse comes in, it doesn't conduct because the cell is not ready to respond to that. It's still refractory. If I draw out that relative refractory period and the underlying conditions are just right, then that PBC falls at the end of that T wave. Now you can have torsades. This is the scenario that happens when someone has a long QT, say hypokalemia, and they're bradycardic and now a PBC falls at the end of that T wave. Because that relative refractory period is a little longer, that's when arrhythmias can occur. What we're doing with medications that we use is we're trying to suppress arrhythmias. Things like sodium channel blockers and potassium channel blockers, we are going to act on a specific component of that action potential to make those arrhythmias less likely to manifest. If I block sodium channels, that results in a decrease in conduction velocity in non-nodal tissue. The faster a cell depolarizes, the more rapidly adjacent cells will become depolarized. That's what we call gap junctions. Gap junctions, induction starts in one place and then it just fires through adjacent tissue very quickly. Now the arrhythmia can propagate very, very quickly. A mechanism for suppressing tachycardias is that we can try to prevent reentry that occurs. If I can use a sodium channel blocker, for example, something like flecainide is one we use a lot in clinical practice, and it has a very strong sodium channel blockade. In doing that, I can disrupt the ability of those cells to respond and allow reentry of those premature atrial beats that come in. You can essentially turn off the ability of those cells to respond to those premature stimuli and that suppresses an arrhythmia from ever manifesting in the first place. By depressing abnormal conduction, we can interrupt reentry mechanisms. Blocking sodium channels affects the conduction in that non-nodal tissue because those sodium channels are a really important part of that action potential. We can contrast that to calcium channels that are very prominent in the nodal tissue. Calcium channel blockers work really well on things like sinus node and AV nodes. We can compare and contrast that way. What else do we think about with antiarrhythmic drugs? We talked about sodium channel blockers and how they work. Potassium channel blockers are the other things we use, things like amiodarone, which is a class three antiarrhythmic. These drugs block potassium channels and it slows the phase three of repolarization and increases the action potential duration. By increasing the absolute refractory period, then we increase the QTC. Some sodium channel blockers also increase the absolute refractory period by prolonging the inactivation state of fast sodium channels. Drugs that increase the absolute refractory period work by disrupting reentrant circuits that lead to tachyarrhythmias. They just do it in a slightly different way. We're drawing out that action potential. We're increasing the absolute refractory period, which is a good thing as long as we don't go too far. Antiarrhythmic drugs alter the absolute refractory period and therefore they decrease cellular excitability. Other things that can be abnormal with the action potential that can be potentially pathologic include triggered activity. When we talk a bit more later in the series about ventricular arrhythmias, we'll discuss some of these in more detail, so this concept will come back. If there's a marked prolongation of a cardiac action potential and then the underlying situation is just right, like there's bradycardia or hypokalemia or there's a long QT, this is when we can have what are called early after depolarizations. That occurs in phase two or phase three. This is some sort of triggered activity that occurs when abnormal action potentials are triggered by a preceding action potential and can result in arrhythmias. The abnormal impulses that you'll see are spontaneous. They're spontaneous depolarizations that occur later and that's why we call these after depolarizations. We think about this as due to things like sometimes ischemia can contribute to this, but certainly things like hypokalemia and a long QT syndrome are the ones that we consider most often. Ischemia acts slightly differently. Ischemia can make contractile cardiac cells irritable. Ischemia results in more open potassium channels and this makes the resting membrane potential less negative or closer to threshold. This means that cell is more likely to respond to a stimulus. There's increased excitability or spontaneously discharge because there's increased automaticity. Faster repolarization in phase three means there's a shorter refractory period and that cell is more likely to respond to a premature beat, which can ultimately potentially lead to torsades. If you see a patient who has things like polymorphic VT or torsade to point, we think about the potential for ischemia and we also consider the potential for things like bradycardia and a prolonged QT interval. And we think about those things because of the abnormal pathophysiology that I hope you feel a bit better about understanding after this lecture. So here are some references that I used for this lecture. And that concludes our discussion of the cardiac electrical conduction system and anatomy and physiology. Thank you.

cardiac conduction system

sinus node

AV node

bundle of His

Purkinje fibers